Guselkumab provides sustained domain-specific and comprehensive efficacy using composite indices in patients with active psoriatic arthritis.

OBJECTIVES: To evaluate the efficacy of guselkumab for the treatment of active PsA utilizing composite indices. METHODS: Data were pooled from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies. In both studies, patients were randomized 1:1:1 to subcutaneous guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then Q8W; or placebo Q4W with crossover to guselkumab 100 mg Q4W at week 24. Composite indices used to assess efficacy through week 52 included Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA), and very low disease activity (VLDA). Through week 24, treatment failure rules were applied. Through week 52, non-responder imputation was used for missing data. RESULTS: Greater proportions of guselkumab- than placebo-treated patients achieved DAPSA low disease activity (LDA) and remission, PASDAS LDA and VLDA, MDA, and VLDA at week 24 vs placebo (all unadjusted P < 0.05). At week 52, in the guselkumab Q4W and Q8W groups, respectively, response rates were as follows: DAPSA LDA, 54.2% and 52.5%; DAPSA remission, 18.2% and 17.6%; PASDAS LDA, 45.3% and 41.9%; PASDAS VLDA, 16.9% and 19.5%; MDA, 35.9% and 30.7%; and VLDA, 13.1% and 14.4%. In the placebo-crossover-to-guselkumab group, response rates for all composite indices increased after patients switched to guselkumab, from week 24 through week 52. CONCLUSION: Treatment with guselkumab provided robust and sustained benefits across multiple PsA domains through 1 year, indicating that guselkumab is an effective therapy for the diverse manifestations of PsA. TRIAL REGISTRATION: NCT03162796; NCT03158285.

Relationships Between Pulmonary Function and Composite Indices of Femoral Neck Strength in Korean Men (KNHANES IV).

BACKGROUND: Despite the close relationship between osteoporosis and chronic pulmonary diseases, few studies have evaluated relationships between pulmonary functions and bone quality. We investigated associations between pulmonary function test results and femoral neck strength indices (SIs) in Korean men. METHODS: This population-based, cross-sectional study was conducted using data from the Korea National Health and Nutrition Examination Survey IV on 936 men aged ≥ 19 years. Pulmonary functions (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1]) were measured using a dry rolling seal spirometer. Femoral neck SIs, relative to load, were calculated by hip dual-energy X-ray absorptiometry for compression strength index (CSI), bending strength index (BSI), and impact strength index (ISI). RESULTS: The 443 (47.3%) of the 936 men were current smokers. FVC, FVC percentage with respect to the expected normal value, FEV1, and FEV1 percentage with respect to the expected normal value (FEV1p) were positively associated with CSI and BSI after adjusting for confounders, including smoking history (ß = 0.003-0.223, P = 0.005-0.036). FEV1 and FEV1p were positively associated with ISI (ß = 0.000-0.014, P = 0.010-0.025). Of components of femoral neck SIs, bone mineral density was correlated with FEV1 and FEV1p (ß = 0.001-0.037, P = 0.017-0.019). After adjusting for all confounders, all femoral neck SIs increased with FVC quintiles (P for trends = 0.001-0.012), and CSI and BSI increased with FEV1 quintiles (P for trends = 0.034-0.043). CONCLUSION: Reduced pulmonary function was correlated with reduced femoral neck strength, even after adjusting for smoking history in Korean men. Femoral neck SIs might be useful tools for evaluating bone health in men with reduced pulmonary function.

Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials.

OBJECTIVE: Data from two double-blind, randomized, Phase III studies were analysed to investigate the ability of Routine Assessment of Patient Index Data 3, DAS28 (CRP), modified (M)-DAS28 (CRP) and Simplified or Clinical Disease Activity Indices to predict structural damage progression in RA. METHODS: This post hoc analysis included data from the 2-year Abatacept vs adaliMumab comParison in bioLogic-naïvE RA subjects with background MTX (AMPLE) trial in biologic-naïve patients with active RA (<5 years) and an inadequate response to MTX, and the 12-month treatment period of the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial in MTX-naïve patients with early RA (⩽2 years) and poor prognostic indicators. Adjusted logistic regression analysis assessed the relationship between baseline disease activity and structural damage progression (defined as change from baseline greater than the smallest detectable change) at 12 and 24 months in AMPLE and 6 and 12 months in AVERT. Areas under the receiver operating characteristic curves for the impact of baseline disease activity on structural damage progression were calculated. RESULTS: Adjusted logistic regression analyses included all randomized and treated patients in AMPLE (N = 646) and those who received abatacept plus MTX or MTX monotherapy in AVERT (N = 235). Baseline Routine Assessment of Patient Index Data 3, DAS28 (CRP) and M-DAS28 (CRP) scores significantly predicted structural progression at months 12 and 24 in AMPLE (P < 0.05) and months 6 and 12 in AVERT (P < 0.01), and were stronger predictors than Simplified or Clinical Disease Activity Indices. CONCLUSION: In this post hoc analysis of two patient populations with RA, Routine Assessment of Patient Index Data 3, DAS28 (CRP) and M-DAS28 (CRP) were good at predicting structural damage. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov: NCT00929864 (AMPLE); NCT01142726 (AVERT).

An integrative analytical model for the water-energy-food nexus: South Africa case study.

The missing link between cross-sectoral resource management and full-scale adoption of the water-energy-food (WEF) nexus has been the lack of analytical tools that provide evidence for policy and decision-making. This study defined WEF nexus sustainability indicators, from where an analytical model was developed to manage WEF resources in an integrated manner using the Analytic Hierarchy Process (AHP). The model established quantitative relationships among WEF sectors, simplifying the intricate interlinkages among resources, using South Africa as a case study. A spider graph was used to illustrate sector performance as related to others, whose management is viewed either as sustainable or unsustainable. The model was then applied to assess progress towards the Sustainable Development Goals in South Africa. The estimated integrated indices of 0.155 and 0.203 for 2015 and 2018, respectively, classify South Africa's management of resources as marginally sustainable. The model is a decision support tool that highlights priority areas for intervention.

Measuring the sustainability of a natural system by using multi-criteria distance function methods: Some critical issues.

There is an important body of literature using multi-criteria distance function methods for the aggregation of a battery of sustainability indicators in order to obtain a composite index. This index is considered to be a proxy of the sustainability goodness of a natural system. Although this approach has been profusely used in the literature, it is not exempt from difficulties and potential pitfalls. Thus, in this paper, a significant number of critical issues have been identified showing different procedures capable of avoiding, or at least of mitigating, the inherent potential pitfalls associated with each one. The recommendations made in the paper could increase the theoretical soundness of the multi-criteria distance function methods when this type of approach is applied in the sustainability field, thus increasing the accuracy and realism of the sustainability measurements obtained.

A reduced 12-joint ultrasound examination predicts lack of X-ray progression better than clinical remission criteria in patients with rheumatoid arthritis.

To study the predictive value of clinical remission definitions and ultrasound (US) examination on X-ray progression in rheumatoid arthritis (RA). This was an observational prospective multicenter 1-year follow-up cohort of RA patients with moderate disease activity (3.2 < DAS28 ≤ 5.1) who started anti-TNF therapy. DAS28ESR, DAS28CRP, SDAI, CDAI, and ACR/EULAR remission criteria were applied and reduced 12-joint US examination was performed at baseline and at 6 and 12 months. At baseline and month 12, radiographs of hands and feet were obtained in a subset of patients. A blind independent reader scored radiographs. X-ray progression was defined as Sharp van der Heijde change score >1 and no progression was defined as ≤0. 319 of 357 patients completed the study; patients had a mean (SD) age of 53.5 (13.1) years, with a disease duration of 7.5 (7.1) years. Laboratory, clinical, and US values significantly improved at month 6, except CRP, with additional improvement at month 12. Remission and low disease activity rates increased at follow-up. In the subset of 115 patients with radiological studies, clinical remission by any definition was not significantly associated with X-ray progression. Patients without PD signal at baseline and month 6 were a lower risk of X-ray progression than patients with PD signal, OR 0.197 (95% CI 0.046-0.861) and 0.134 (95% CI 0.047-0.378), respectively. Absence of PD signal, but not clinical remission predicts lack of X-ray progression. A feasible 12-joint US examination may add relevant information to RA remission criteria.

Structured deep embedding model to generate composite clinical indices from electronic health records for early detection of pancreatic cancer.

The high-dimensionality, complexity, and irregularity of electronic health records (EHR) data create significant challenges for both simplified and comprehensive health assessments, prohibiting an efficient extraction of actionable insights by clinicians. If we can provide human decision-makers with a simplified set of interpretable composite indices (i.e., combining information about groups of related measures into single representative values), it will facilitate effective clinical decision-making. In this study, we built a structured deep embedding model aimed at reducing the dimensionality of the input variables by grouping related measurements as determined by domain experts (e.g., clinicians). Our results suggest that composite indices representing liver function may consistently be the most important factor in the early detection of pancreatic cancer (PC). We propose our model as a basis for leveraging deep learning toward developing composite indices from EHR for predicting health outcomes, including but not limited to various cancers, with clinically meaningful interpretations.

Promoting the culture of key performance indicators (KPIs) among primary health care staff at health district level: An intervention study.

Recently, identifying performance indicators and developing measurement frameworks have become crucial concerns. Our study first sought to analyze service statistics of Primary Health Care (PHC) facilities for the years 2017 and 2018 to develop PHC key performance indicators (KPI).This was then followed by a thorough discussion of these KPIs with staff and service providers. Finally, re-rating these PHC (KPI) changes by analyzing service statistics infographs for 2017 and 2018 relative to 2019. El-Aiat Health District-Giza Governorate and its 15 PHC facilities served as the study's setting. A quasi-experimental intervention design was used based on operation research with quantitative and qualitative data analysis. The pre-test consisted of a mathematical analysis of service and vital statistics for 2017 and 2018 to calculate composite indices and create infographs (simple colored matrices) for these indices. The intervention included two discussion meetings (2 h each). It included reviewing the Performance Knowledge Matrices (infographs) with the service providers for subsequent problem specification, solving, and suggestion extraction to enhance performance. The SWOC (Strengths, Weaknesses, Opportunities, and Challenges) framework was used to analyze the qualitative data extracted from these conversations. Among the identified flaws were a deficiency in the number of physicians and nurses, inadequate training, insufficient work environments, and a lack of moral appreciation and recognition for the staff. The proposed solutions include providing health education services by nurses and follow-up services in certain units via home visits and mobile clinics. Post-test also entailed analyzing service and vital statistics for 2019 and redisplaying KPI infographics. Four of fifteen PHC facilities achieved a positive response based on the staff-suggested info-action-based intervention, according to our findings after comparing data for the pre-intervention and post-intervention periods of 2017-2018 and 2019. We concluded that reviewing the information derived from the "knowledge performance colored matrix" inspired district and PHC service providers to identify their weaknesses (avoided them as much as possible) and their strengths (practiced the solutions they suggested themselves) in the meetings which eventually improved their performance. Ultimately, the outcome scores and impact indicators of the provided PHC services were enhanced.

The Child and Adolescent Thriving Index 1.0: Developing a Measure of the Outcome Indicators of Well-Being for Population Health Assessment.

The well-being of children and adolescents is emerging as an area of interest for population health measurement. Previous approaches assessing national and state trends in well-being have relied on composite indices. However, these methodologies suffer from several weaknesses. This paper develops an improved index for the United States that is measurable with existing population-data resources. It derives the appropriate weights for items in this index using a longitudinal panel of 2,942 children in the Panel Study of Income Dynamics. Candidate component measures are selected for the index based on their demonstrated association with several subjective scales assessed during young adulthood. The final index demonstrates that a broad range of measures indicate higher levels of population-level well-being. The predictive validity of the index for outcomes during young adulthood is also assessed: a one-standard-deviation increase in the index score is associated with a 7.9-percentage-point decrease [95% CI: 5.9 - 9.8] in ever reporting fair or poor health, a 6.3-percentage-point decrease [95% CI: 4.6 - 8.0] in ever reporting depression, and a 17.2% [95% CI: 13.7% - 20.5%] increase in peak earnings. These values for predictive validity are slightly higher than those of existing methodologies. We also find that incorporating contextual indicators from childhood and adolescence does not substantively improve predictive validity. Policy-makers and government agencies interested in population-level well-being of children and adolescents can continue to use existing indices as reasonable proxies, but should also commit to upgrading data systems to make them more child-centric in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s12187-022-09962-0.

Analysis of Crisis Phenomena in the Russian Economy Using Fast Indicators of Economic Security.

This article shows the possibility of applying short-term (fast) indicators of economic security to analyze crisis phenomena in the economy of Russia. The system includes the indicators adopted in the Strategy for the Economic Security of the Russian Federation up to 2030. It is proposed to jointly analyze these indicators through new nonlinear normalizing functions that contain their threshold and target values as parameters. The fast indicators system is used to analyze four economic crises in Russia, including their prerequisites and the pace and depth of the recession and subsequent recovery of the real economy and other sectors, such as the financial and social sectors, and foreign trade. Integral indices are synthesized for these sectors, the composite index of economic security is calculated, and the patterns of their joint movement are considered. The RTS index is singled out among the forward-looking indices that can be potential forerunners of a crisis.

Residual Disease Activity and Associated Factors in Psoriatic Arthritis.

OBJECTIVE: Remission or low disease activity should be the treatment target of psoriatic arthritis (PsA). However, residual disease activity (RDA) in some domains could persist. The aim of this study was to assess RDA and its associated factors in a group of patients with PsA. METHODS: Patients with PsA were enrolled if they satisfied ClASsification for Psoriatic ARthritis (CASPAR) criteria with > 6 months' followup and achieved a status of low disease activity (LDA), minimal disease activity (MDA), or remission [Disease Activity Index for PsA (DAPSA) remission or very low disease activity (VLDA)]. RDA was assessed by the percentage of patients who had, although in LDA or remission, tender and/or swollen joints > 1, Leeds Enthesitis Index > 1, Health Assessment Questionnaire > 0.5, Psoriasis Area Severity Index (PASI) > 1, patient's global assessment > 20, physician visual analog scale (VAS) > 20, and VAS pain > 15. Associated factors of RDA were also assessed. RESULTS: Of 113 enrolled patients, 78 (69%) were in MDA. Moreover, DAPSA remission was observed in 46 (40.7%) while VLDA only in 32 (28.3%) of patients with PsA. VLDA seems to be the most stringent criterion, with a minimal RDA only in the VAS physician in 1 patient (3.1%) and none in the different domains, while patients in MDA had RDA in tender joints (14.1%), VAS pain (29.4%) and PASI > 1 or body surface area (BSA) > 3% (17.9%). Of note, although patients in DAPSA remission show a very low rate of RDA in almost all domains, 12 (26%) of them show a PASI > 1 or BSA > 3%. Finally, LDA shows RDA in higher percentages, mainly in patient-reported outcomes, tender joints, and skin domain. CONCLUSION: RDA can be recognized in patients with PsA. VLDA seems to be the most stringent composite index to identify patients in the absence of RDA.

Impact of Comorbidities on Disease Activity, Patient Global Assessment, and Function in Psoriatic Arthritis: A Cross-Sectional Study.

INTRODUCTION: The aim of this study was to evaluate the impact of comorbidities on disease activity, patient's impact of the disease, patient global assessment, and function in psoriatic arthritis (PsA). METHODS: Consecutive PsA patients were enrolled in this cross-sectional study. During the visit, the patients underwent a complete physical examination and clinical/laboratory data were collected, including type and number of comorbidities, recorded as simple comorbidity count (SCC). Disease activity was assessed using the Disease Activity Score for Psoriatic Arthritis (DAPSA) and the Minimal Disease Activity (MDA) was also evaluated. The Psoriatic Arthritis Impact of Disease (PsAID), the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Patient Global Assessment of disease activity (PtGA) were also collected. RESULTS: A total of 144 patients were enrolled. At least one comorbidity was registered in 104 (72.2%) patients. The SCC was associated with DAPSA (ß = 1.48, p = 0.013), PsAID (ß = 0.41, p < 0.01), HAQ-DI (ß = 0.11, p < 0.01) and PtGA (ß = 0.50, p < 0.01). The comorbidities that showed an impact on outcome measures were anxiety and fibromyalgia (FM). Anxiety showed an impact on DAPSA (ß = 14.46, p < 0.001), PsAID (ß = 1.98, p = 0.039) and HAQ-DI (ß = 0.54, p = 0.036). FM showed an impact on DAPSA (ß = 6.46, p = 0.025), PsAID (ß = 2.88, p < 0.001), HAQ-DI (ß = 0.70, p < 0.001), PtGA (ß = 2.00, p = 0.014), and MDA (ß = - 2.79, p = 0.01). The median PtGA value was different among patients with different numbers of comorbidities. CONCLUSIONS: This study showed that comorbidities, either as a simple comorbidity count number or as single comorbidity, might have an impact on the main domains affecting PsA patients in real clinical practice.

Inhibition of radiographic progression across levels of composite index-defined disease activity in patients with active psoriatic arthritis treated with intravenous golimumab: results from a phase-3, double-blind, placebo-controlled trial.

BACKGROUND: In the GO-VIBRANT trial of intravenous golimumab in psoriatic arthritis (PsA), golimumab significantly inhibited radiographic progression. In post hoc analyses, we evaluated changes in total PsA-modified Sharp/van der Heijde scores (SHS) across levels of composite index-defined disease activity following treatment. METHODS: In this phase-3, double-blind, placebo-controlled trial, 480 bio-naïve patients with active PsA randomly received intravenous golimumab 2 mg/kg (N = 241; week 0, week 4, every 8 weeks [q8w]) or placebo (N = 239; week 0, week 4, week 12, week 20) followed by golimumab (week 24, week 28, q8w) through week 52. Week 24 and week 52 SHS changes in patient subgroups, defined by levels of disease activity as assessed by several composite measures (minimal disease activity [MDA], very low disease activity [VLDA], Psoriatic ArthritiS Disease Activity Score [PASDAS], Disease Activity in Psoriatic Arthritis [DAPsA], Clinical Disease Activity Index [CDAI]), were evaluated post hoc in 474 patients with evaluable radiographic data. Partially (last-observation-carried-forward methodology) and completely (nonresponder methodology) missing data were imputed. RESULTS: Across indices, golimumab-treated patients demonstrated less radiographic progression than placebo-treated patients, regardless of disease activity state achieved via golimumab, from week 0 to 24 (e.g., mean changes in PsA-modified SHS were - 0.83 vs. 0.91, respectively, in patients achieving MDA and - 0.05 vs. 1.49, respectively, in those not achieving MDA). Treatment differences observed at week 24 persisted through week 52, despite placebo-randomized patients crossing over to golimumab at week 24 (e.g., mean changes in PsA-modified SHS from week 0 to 52 for golimumab- vs. placebo→golimumab-treated patients achieving MDA were - 1.16 vs. 1.19, respectively) and regardless of whether low disease activity was achieved (0.03 vs. 1.50, respectively, in those not achieving MDA). Consistent patterns were observed for disease activity assessed using VLDA, PASDAS, DAPsA, and CDAI composite endpoints. CONCLUSIONS: The extent of structural damage inhibition afforded by up to 1 year of intravenous golimumab treatment paralleled levels of PsA activity, with greater progression of structural damage observed in patients with sustained higher disease activity. Among patients not achieving low levels of disease activity across several composite indices, golimumab-randomized patients appeared to exhibit far less progression of structural damage than placebo-randomized PsA patients, illustrating a potential disconnect between responses, wherein golimumab can inhibit structural damage independent of clinical effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT02181673. Registered 04 July 2014.

Assessing the performance of the least developed countries in terms of the Millennium Development Goals.

This article presents a proposal for assessing the progress of least developed countries towards the achievement of the Millennium Development Goals over the period 2000-2015. Composite indices are built to perform spatial and temporal benchmarking relying on the P2 Distance method. The results are contrasted with other indices developed under a multi-criterion approach with a double reference point. The main findings are that all the countries have improved their situation and country disparities have been reduced. Cambodia and Ethiopia have registered the best trends and South Sudan and Timor-Leste show the worse performance. Considering the position in the 2015 ranking, Rwanda and Bhutan performed the best, while Somalia and Chad rank in the last position. Having now reached the end of the Millennium Development Goals period, the gap with respect to the world average indicates that much work remains to be done in the 2030 Agenda for Sustainable Development.

Comparison of Composite Indices Tailored for Psoriatic Arthritis Treated with csDMARD and bDMARD: A Cross-sectional Analysis of a Longitudinal Cohort.

OBJECTIVE: In a complex disease such as psoriatic arthritis (PsA), several methods are available to define remission or low disease activity (LDA), including the assessment of different clinical features. The aim of this study was to compare the composite indices tailored for PsA in patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and biological DMARD (bDMARD). METHODS: Patients with PsA classified with the ClASsification criteria for Psoriatic ARthritis criteria and with > 6 months followup treated with first csDMARD and bDMARD were consecutively enrolled. To assess disease activity, composite indices tailored for PsA were used, such as the Disease Activity Index for Psoriatic Arthritis (DAPSA), clinical DAPSA (cDAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA) 5/7, and MDA 7/7. DAPSA and cDAPSA score ≤ 4, MDA 7/7, and PASDAS ≤ 1.9 identified remission. MDA 5/7, DAPSA score ≤ 14, cDAPSA score ≤ 13, and PASDAS < 3.2 identified the MDA and LDA criteria. RESULTS: One hundred nine patients with PsA were enrolled: 79 patients were receiving stable treatment with bDMARD and 30 with csDMARD. Overall, 28 (25.6%), 23 (21.1%), 19 (17.4%), and 13 patients (11.9%) were in cDAPSA remission, DAPSA remission, MDA 7/7, and PASDAS ≤ 1.9, respectively. Moreover, 54 (49.5%), 80 (73.3%), 79 (72.3%), and 38 patients (34.8%) were in MDA 5/7, DAPSA LDA, cDAPSA LDA, and PASDAS LDA. Patients treated with bDMARD had significantly lower median DAPSA, cDAPSA, and PASDAS score than patients treated with csDMARD. CONCLUSION: Patients with PsA receiving bDMARD are more likely to achieve a status of MDA and remission when compared with csDMARD. PASDAS ≤ 1.9 and MDA 7/7 seem to be stringent remission criteria.